ChangesinautonomicneuralactivitydonotusuallychangetheheartratebyalteringthethresholdlevelofVminthenodalpacemakercells.However,certainantiarrhythmicdrugs,suchasquinidineandprocainamide,doshiftthethresholdpotentialoftheautomaticcellstolessnegativevalues.
cells in the heart. In the pacemaker cells of the SA node, at least three ionic currents mediate the slow diastolic depolarization: (1) an outward K+ current, iK; (2) a hyperpolarization-induced inward current, if; and (3) an inward Ca++ current, ICa (
Fig. 16.19
The repetitive firing of the pacemaker cell begins with the iK current. Efflux of K+ tends to repolarize the cell after the upstroke of the action potential. K+ continues to move out well beyond the time of maximal repolarization, but its efflux diminishes throughout phase 4 (see
Fig. 16.19 ). As the current diminishes, its opposition to the depolarizing effects of the two inward currents (if and iCa) also gradually decreases. The progressive diastolic depolarization is mediated by the if and iCa currents, which oppose the repolarizing effect of the iK current.
The inward current if is activated near the end of repolarization and is carried mainly by Na+ through specific channels that differ from the fast sodium channels. The current was dubbed “funny” because its discoverers had not expected to detect an inward Na+ current in pacemaker cells at the end of repolarization. This current is activated as the membrane potential becomes hyperpolarized beyond −50 mV. The more negative the membrane potential at this time, the greater the activation of if.
The second current responsible for diastolic depolarization is the inward rectifying Ca++ current, iCa. This current is activated toward the end of phase 4 as the membrane potential reaches a value of approximately −35 mV (see
Fig. 16.19 ). Once the calcium channels are activated, influx of Ca++ into the cell increases. This influx accelerates the rate of diastolic depolarization, which then leads to the action potential upstroke. A decrease in extracellular •Fig. 16.19 Themembranepotentialchanges(blue trace, top half) thatoccurinsinoatrialnodecellsareproducedbythreeprincipalcurrents(green trace, bottom half): theinwardCa++ current(iCa);ahyperpolarization-inducedinwardcurrent(if),andanoutwardK+ current(iK).Thethinnoisygreen trace showsnetmembranecurrentandtheapproximatetimecourseoftherepolarizingoutwardK+ current(iK),thehyperpolarization-inducedinwardcurrent(if),andtheL-typeCa++ current(iCa).Thethick bold red line inthecurrenttraceindicatesthemagnitudeanddirectionofestimatedIf.(RedrawnfromvanGinnekenACG,GilesW.J Physiol. 1991;434:57.)